Besivance

CLINICAL PHARMACOLOGY

Mechanism of Action

Besifloxacin is a fluoroquinolone antibacterial.

Pharmacokinetics

Plasma concentrations of besifloxacin were measured in adult
patients with suspected bacterial conjunctivitis who received Besivance®
bilaterally three times a day (16 doses total). Following the first and last
dose, the maximum plasma besifloxacin concentration in each patient was less
than 1.3 ng/mL. The mean besifloxacin Cmax was 0.37 ng/mL on day 1 and 0.43
ng/mL on day 6. The average elimination half-life of besifloxacin in plasma
following multiple dosing was estimated to be 7 hours.

Microbiology

Besifloxacin is an 8-chloro fluoroquinolone with a N-1
cyclopropyl group. The compound has activity against Gram-positive and
Gram-negative bacteria due to the inhibition of both bacterial DNA gyrase and
topoisomerase IV. DNA gyrase is an essential enzyme required for replication,
transcription and repair of bacterial DNA. Topoisomerase IV is an essential
enzyme required for partitioning of the chromosomal DNA during bacterial cell
division. Besifloxacin is bactericidal with minimum bactericidal concentrations
(MBCs) generally within one dilution of the minimum inhibitory concentrations
(MICs).

The mechanism of action of fluoroquinolones, including
besifloxacin, is different from that of aminoglycoside, macrolide, and
β-lactam antibiotics. Therefore, besifloxacin may be active against
pathogens that are resistant to these antibiotics and these antibiotics may be
active against pathogens that are resistant to besifloxacin. In vitro studies
demonstrated crossresistance between besifloxacin and some fluoroquinolones.

In vitro resistance to besifloxacin develops via
multiple-step mutations and occurs at a general frequency of < 3.3 x 10-10
for Staphylococcus aureus and < 7 x 10-10 for Streptococcus
pneumoniae.

Besifloxacin has been shown to be active against most
isolates of the following bacteria both in vitro and in conjunctival infections
treated in clinical trials as described in the INDICATIONS AND USAGE section:

Clinical Studies

In a randomized, double-masked, vehicle controlled,
multicenter clinical trial, in which patients 1-98 years of age were dosed 3
times a day for 5 days, Besivance® was superior to its vehicle in patients with
bacterial conjunctivitis. Clinical resolution was achieved in 45% (90/198) for
the Besivance® treated group versus 33% (63/191) for the vehicle treated group
(difference 12%, 95% CI 3% - 22%). Microbiological outcomes demonstrated a
statistically significant eradication rate for causative pathogens of 91%
(181/198) for the Besivance® treated group versus 60% (114/191) for the vehicle
treated group (difference 31%, 95% CI 23% - 40%). Microbiologic eradication
does not always correlate with clinical outcome in anti-infective trials.

Last reviewed on RxList: 10/26/2012
This monograph has been modified to include the generic and brand name in many instances.